Imatinib for Cytomegalovirus Prophylaxis and Treatment After Allogeneic Hematopoietic Stem Cell Transplantation

Patients Who Have Received Allo-HSCT Clinical Trial

Official title:

A Randomization, Double Blind, Multicenter Phase II Clinical Trial to Evaluate the Imatinib for Prophylaxis of CMV Infection After Allogeneic Hematopoietic Stem Cell Transplantation

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03343600
• Other study ID #: 201707076MIPB
• Status: Terminated
• Phase: Phase 2
• Start date: November 9, 2017
• Est. completion date: August 31, 2019

Study information

• Verified date: September 2019
• Source: National Taiwan University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study aim at examining whether blocking platelet-derived growth factor receptor-α by imatinib lowers the risk of post-allogeneic hematopoietic stem cell transplantation CMV infection.

Description:

This is a randomized, double-blind, multicenter phase II clinical trial. In the trial, post-allo-HSCT patients with signs of bone marrow engraftment and without evidence of CMV reactivation will be enrolled. All enrolled patients will be monitored for their blood CMV DNA copy numbers by Q-PCR and safety throughout the trial. In addition to their routine post-allo-HSCT care, eligible patients will receive imatinib (100mg/tablet, 2 tablets daily) or placebo (2 tablets daily) administration after myeloid engraftment (defined as absolute neutrophil count higher than 500 for three consecutive days). While receiving the trial therapy, patients will have a regular CMV surveillance every week by the quantification of plasma CMV DNA copies. During the administration of the investigational drugs, other concomitant anti-CMV prophylaxis treatments are prohibited. When a patient has any signs suggesting CMV infection that the treating physician determines that an anti-CMV therapy is indicated, the patient will be defined as failure of prophylaxis for the efficacy evaluation. Whether the conventional anti-CMV therapy is started or not, the investigational drugs with imatinib or placebo will be continued till at least Day+100 unless the patient is defined as prophylaxis failure or withdraws from the study including personal reasons, early mortality, disease recurrence after transplantation, pregnancy, or the investigator decides that the subject should be withdrawn for safety reasons or physical conditions.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: August 31, 2019
• Est. primary completion date: August 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

• Adult patients (Age ? 20) who received the first allo-HSCT are eligible;

• Patients with underlying disease of acute leukemia in morphological remission, or myelodysplastic syndrome;

• Received allo-HSCT with HLA-matched sibling or unrelated donors (at least 8/8 match for HLA-A/B/C/DR);

• Evidence of post-transplantation neutrophil engraftment: absolute neutrophil count > 500/mm3 for at least 3 consecutive days;

• No detectable CMV infection before study enrollment: negative plasma CMV DNA surveillance within passing 2 weeks;

• No previous post-transplantation anti-CMV therapy and no planned prophylactic anti-CMV therapy;

• The patients has the ability to swallow tablets

Exclusion Criteria:

• They have renal insufficiency: serum creatinine > 2.5 mg/dL;

• They have hepatic dysfunction: serum alanine or aspartate aminotransferase levels of > 5 times the upper limit of the normal range or a serum total bilirubin of > 3 mg/dL;

• Patients with history of HIV infection;

• Unstable post-BMT condition or other medical condition deemed not appropriate to be included to this study as judged by investigator;

• Life expectancy less than 3 months;

• Unwillingness or unable to give consent;

• Patients with diseases that are positive for t(9;22) or BCR-ABL fusion gene.

Related Conditions & MeSH terms

• Patients Who Have Received Allo-HSCT

Intervention

Drug:
• Imatinib
Imatinib 100 mg/tablet, 2 tablets daily
• Placebo
Placebos 2 tablets daily

Locations

Country	Name	City	State
Taiwan	Tzu Chi General Hospital	Hualien City
Taiwan	Far Eastern Memorial Hospital	New Taipei City
Taiwan	National Cheng Kung Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Tri-Service General Hospital	Taipei

Sponsors (5)

Lead Sponsor	Collaborator
National Taiwan University Hospital	Far Eastern Memorial Hospital, Hualien Tzu Chi General Hospital, National Cheng-Kung University Hospital, Tri-Service General Hospital

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants free from initiating conventional anti-CMV treatment by Day+100 after allo-HSCT.	Investigator determined whether anti-CMV treatment is needed or not based on clinical judgment no matter therapeutic or preemptive treatment. Symptomatic CMV infection or CMV organ disease was defined as described by Ljungman et al., 2002.	From first dosing to 100 days after allo-HSCT (Day+100)
Secondary	Number of treatment-related adverse events (AE) by Day+100 after allo-HSCT.	Safety profile will be evaluated according to treatment-related adverse events (AE) per CTCAE 4.03 version.	From first dosing to 100 days after allo-HSCT (Day+100)
Secondary	Time to onset of CMV reactivation defined by peripheral blood CMV copies by Day+100 after allo-HSCT.	The peripheral blood CMV DNA copy numbers (copies/mL) were determined using a commercial kit with PCR method following its protocol. The CMV copy numbers are monitored on a weekly basis.	From first dosing to 100 days after allo-HSCT (Day+100)
Secondary	Time to onset of CMV disease diagnosed by investigator by Day+100 after allo-HSCT.	The diagnosis of CMV disease is based on clinical practice and the invasive procedure was encouraged to make the definite diagnosis. The reference to CMV organ disease definition was described by Ljungman et al., 2002.	From first dosing to 100 days after allo-HSCT (Day+100)
Secondary	Number of participants who had progressive hematological disease within 6 months after allo-HSCT.	Defined as any subject that is known to have a progressive hematological disease.	6 months post-transplant
Secondary	Number of participants who died within 6 months after allo-HSCT.	Defined as any subject that is known to be dead.	6 months post-transplant